The field of the invention is treatment of diseased cells.
Today, progress has been made against many diseases, including cancers, bacterial and viral infections. In the case of cancers, for example, surgery, chemotherapy, radiation, and cytokine therapies have all made significant contributions in either curing the conditions, or at least prolonging the lives of the patients. Similarly, antibiotics have made significant inroads against bacterial infections, and even viral infections have been successfully treated with various compounds such as ribavirin and interferon. Despite all of these advancements, however, there continues to be a need for more effective treatments.
One promising avenue is the use of cytokines. Cytokines are relatively small molecules having broad antiviral, antiproliferative and immunomodulatory effects. One particular class of cytokines, the interferons (IFN), are especially interesting, having been recognized as providing antiproliferative activities, as well as for antiviral and immunoregulatory activities (Fleishman, C M et al., xe2x80x9cDifferential Antiproliferative Activities of IFNs xcex1, xcex2 and xcex3: Kinetics of Establishment of Their Antiproliferative Effects and The Rapid Development of Resistance to IFNs xcex1 and xcex2xe2x80x9d, J. Bio. Regulators and Homeostatic Agents, 1988, Vol. 2, no. 4, pp 173-185). In the field of cancer, for example, studies have concluded that in vivo administration of interferons have some efficacy for a number of neoplastic conditions, including hairy cell leukemia, Kaposi""s sarcoma in AIDS, chronic granulomatous disease, chronic myelogenous leukemia, non-Hodgkin""s lymphoma, multiple myeoloma, cutaneous T cell lymphoma, malignant melanoma, renal cell carcinoma, carcinoid, and cervical intraephithelial neoplasia. Unfortunately, in vivo administration of cytokines is generally less efficacious with respect to treating most cancers as cytotoxic drugs, radiation, and chemotherapy. In addition, in vivo use of cytokines (i.e. intravenous or other direct administration) has detrimental side effects.
Ex vivo use of cytokines has also been studied, and some researchers have achieved moderately promising results with ex vivo treatment using IL-2 (see e.g., Steven Rosenberg""s work). On the other hand, ex vivo treatment of diseased cells with IFN has not been effective, and work in this area has more or less been terminated.
In hindsight, such failure should have been expected. With respect to short-term exposures, studies show that subjecting cells to interferon for 24 hours or less does not stimulate presentation of surface antigens. Since antigen presentation is generally needed to trigger an effective immune response, it follows that such treatment would provoke little or no immune response. With respect to long-term exposure, it is generally recognized that interferon treatment inhibits the growth of cells, and as such one would expect that tumor cells would not be able to be cultured long term in the presence of interferon. Still further, it is known that cells harvested from an organism rapidly accommodate to their ex vivo environment, and tend to present antigens that are ever more modified as compared with antigens produced by similar cells remaining in vivo. Therefore, one of ordinary skill in the art would conclude that long-term ex vivo exposure of cells to interferon would be detrimental to the overall effectiveness of this treatment. Even further, there is no teaching or suggestion for long-term exposure of cells to interferon.
Thus, there is still a need to provide methods by which cytokines in general, and interferons in particular, can be employed in the ex vivo treatment of diseased cells.
The present invention provides methods for treating diseased cells in a system, and generally comprises removing a sample of the diseased cells from the system, contacting the diseased cells with an interferon for at least 48 hours, and reintroducing the interferon contacted cells into the system.
In one aspect of preferred embodiments, the system is a vertebrate, preferably a human. But it could also be used to treat cancers in pets such as dogs or cats, or other valued animals. In another aspect of preferred embodiments, the diseased cells are afflicted with a cancer, a bacterium, a virus or a fungus. In still other aspects of preferred embodiments, the interferon is a Type 1 interferon, i.e., interferon alpha, interferon beta, interferon tau, interferon omega, or a genetically created recombinant form of interferon such as consensus alpha. In still other aspects of preferred embodiments, the diseased cells are placed in contact with the interferon (or interferons) for a relatively long period of time, such as 36 hours, 48 hours, 72 hours, 5 days, 7 days, 10 days, 14 days, or even longer. In still other aspects of preferred embodiments, the cells reintroduced into the system are at least partially inactivated. In still other aspects of preferred embodiments, the cells can be reintroduced into a system which is at particularly high risk for a given disease, and in that sense act as a vaccine.
Various objects, features, aspects and advantages of the present invention will become more apparent from the following detailed description of preferred embodiments of the invention.